Fribley Andrew M, Xi Yue, Makris Christina, Alves-de-Souza Catharina, York Robert, Tomas Carmelo, Wright Jeffrey L C, Strangman Wendy K
Carman and Ann Adams Department of Pediatrics, Division of Hematology/Oncology and the Molecular Therapeutics Program, Karmanos Cancer Institute, Wayne State University, 421 East Canfield, Detroit, Michigan 48201, United States.
Department of Chemistry and Biochemistry, University of North Carolina Wilmington, 601 South College Road, Wilmington, North Carolina 28403, United States.
ACS Med Chem Lett. 2018 Dec 26;10(2):175-179. doi: 10.1021/acsmedchemlett.8b00473. eCollection 2019 Feb 14.
Spiroimines are a class of compounds produced by marine dinoflagellates with a wide range of toxicity and therapeutic potential. The smallest of the cyclic imines, portimine, is far less toxic than other known members in several animal models. Portimine has also been shown to induce apoptosis and reduce the growth of a variety of cancer cell lines at low nanomolar concentrations. In an effort to discover new spiroimines, the current study undertook a metabolomic analysis of cultures of cyclic imine-producing dinoflagellates, and a new analog of portimine was discovered in which the five-membered cyclic ether is open. Further scrutiny with human oral cavity squamous cell carcinoma (OCSCC) cell lines revealed that the open ring congener was less potent than portimine A but could still lead to the accumulation of apoptotic gene transcripts, fragment genomic DNA, and reduce cancer cell proliferation in the range of 100-200 nM.
螺亚胺是一类由海洋双鞭毛藻产生的化合物，具有广泛的毒性和治疗潜力。最小的环状亚胺——波特亚胺，在几种动物模型中其毒性远低于其他已知成员。波特亚胺还被证明在低纳摩尔浓度下可诱导细胞凋亡并减少多种癌细胞系的生长。为了发现新的螺亚胺，当前研究对产生环状亚胺的双鞭毛藻培养物进行了代谢组学分析，并发现了一种波特亚胺的新类似物，其中五元环醚是开环的。对人口腔鳞状细胞癌（OCSCC）细胞系的进一步研究表明，开环同系物的效力低于波特亚胺A，但在100 - 200 nM范围内仍可导致凋亡基因转录本的积累、基因组DNA片段化，并减少癌细胞增殖。
